Impact of a maternal low protein diet during pregnancy on fetal amino acid availability and kidney development in sheep

Physiology 2012 (Edinburgh) (2012) Proc Physiol Soc 27, PC341

Poster Communications: Impact of a maternal low protein diet during pregnancy on fetal amino acid availability and kidney development in sheep

L. Lloyd1, K. D. Sinclair2, D. Gardner1

1. School of Veterinary Medicine and Science, University of Nottingham, Nottingham, United Kingdom. 2. School of Biosciences, University of Nottingham, Nottingham, United Kingdom.

View other abstracts by:


Introduction: Maternal malnutrition leads to offspring with a greater risk of developing chronic kidney disease. We have previously shown that a maternal low protein, but isoenergetic, diet impacts upon early developmental processes (decreased angiogenesis, increased apoptosis) in the fetal kidney to reduce nephron number in the mature kidney (a 15% reduction). In the current study we used this nutritional paradigm to characterise the nutritional environment of the dam and fetus at 0.44 dGA and relate the nutritional pattern to macro- and microvascular development in the fetal kidney. Methods: Pregnant twin-bearing ewes were fed either a control diet providing adequate dietary protein (control protein, CP [16.9 g/kg/MJ DM]; n=15), or a low protein diet (LP, 8.7g/kg/MJ DM; n=16) from the day of artificial insemination with semen from a single ram (day 0) to day 65 gestation (term, 147 days). Maternal blood samples were taken at fortnightly intervals until day 65 when the ewes and conceptuses were euthanised (barbiturate overdose, 150 mg/kg BW). Tissues were fixed (4% PFA in 0.1M PBS), snap-frozen or a fetal renal vascular corrosion cast was made. Casts were scanned by computed tomography (40µm, Nanotom) and volumetric data quantified. Maternal and fetal plasma and amniotic amino acids were measured by GC-MS. Data are mean [s.e.d] and were analysed by linear mixed-effects models (Genstat v14, VSNi, UK). Results: LP sheep had significantly increased plasma concentrations of glucose, lactate, albumin, total protein and NEFA relative to controls, but decreased urea (e.g. in amniotic fluid; 3497 vs. 6916 [489] µmol/L for LP vs. CP). Maternal plasma osmolality was increased in LP vs. CP (e.g. at day 14 gestation, 320 vs. 285 [10] mosmoles/kg water). The maternal amino acid profile was unaffected by diet but changed with time; however, in fetal plasma and amniotic fluid ornithine concentration was significantly decreased by a maternal LP diet (e.g. in amniotic fluid, 74.2 vs. 109 [±12] µmol/L for LP vs. CP). Fetal kidney vascular casts were not different between treatment groups, but indices of the fetal kidney microvasculature were significantly (P=0.02) reduced in LP vs. CP (e.g. VEGF protein abundance in nephrogenic zone; 0.79 vs. 1.32 [0.14] units). Conclusions: A maternal low protein diet has little effect on maternal or fetal macronutrient balance but has marked effects on specific micronutrients; urea is reduced in the maternal and fetal compartment and this translates to markedly reduced plasma ornithine concentration in fetal plasma and amniotic fluid. A nutritional pathway from maternal low protein, through decreased urea-ornithine to reduced polyamine synthesis and blunted cellular growth is inferred, but remains to be tested.



Where applicable, experiments conform with Society ethical requirements.

Site search

Filter

Content Type